In a recent study of life span in mice with hereditary dwarfism (Ames dwarf mice, df/df), we have discovered that dwarf animals live longer that their normal siblings. This difference is large (greater than 250 days for males and greater than 1 year for females) and highly significant (P less than 0.001). More than 1/2 of female dwarf animals survive to 3 1/2 years of age. The objective of this pilot project is to characterize of Ames dwarf mouse as a novel model for aging research. Specific aims include (i) verifying our initial observations in a large number of mice (100 dwarfs and 100 normals), (ii) pathological studies at gross and microscopic level directed at identifying the cause(s) of death in dwarf and normal animals, and (iii) studies of the effects of growth hormone (GH), thyroid hormone (thyroxine, T4) and prolactin (PRL) on life span of Ames dwarf mice. Studies of the effects of GH, T4, and PRL will test the hypothesis that greater life expectancy of Ames dwarf mice may be specifically related to known hormonal deficits of these animals and may provide some clues as to the mechanisms involved. The proposed studies will involve crossing dwarf mice to transgenic animals expressing GH, under control of the metallothionein promoter, to produce animals in which hereditary GH deficiency is compensated for by transgene expression. Other dwarf animals will receive transplants of pituitaries from normal donors to provide PRL replacement.